These data support four principal findings: 1) Treatment seeking alcoholics without another active substance use disorder had high rates of HCV and high lifetime rates of injection drug use and needle sharing which were not significantly different from those of a treatment seeking population with comorbid cocaine and alcohol dependence, 2) Regardless of recent drinking behavior, HCV infection in this population was associated with a significant upward shift in mean AST, ALT, and GGT values, 3) Again, regardless of recent drinking behavior, this upward shift was also associated with elevations of AST, ALT and GGT above the standard lab cutoff value, and 4) Although there was a paradoxical downward shift in mean CDT, CDT was the only alcohol use biomarker in this sample to remain within the lab cutoff range independent of HCV status.
What is perhaps most interesting in these findings is that regardless of drinking behavior, having HCV appears to lead to significantly higher ALT, AST and GGT lab values and significantly lower CDT values. In contrast, drinking behavior appears to elevate all LFTs in HCV negative subjects. This suggests that LFTs may be most useful as alcohol biomarkers primarily for those without HCV, as the presence of HCV appears to mask any potential variation in LFTs due to alcohol use. As hepatic injury or disease has been shown to elevate GGT (Silva et al. 2004
), ALT and AST (Limdi & Hyde 2003
), it is possible that HCV infection leads to a ceiling effect for these LFTs such that alcohol use produces no further elevation beyond that produced by HCV.
As CDT is the biomarker that is least influenced by hepatic disease in alcoholics (Scouller et al. 2000
), we would not expect to see much impact of HCV on CDT in this study. In fact, supporting the extant literature, CDT levels did not appear elevated in relation to HCV status in our outpatient cohort. CDT in fact was significantly decreased in our HCV seropositive cohort. Despite our attempt to capture our sample in a pre-acute recovery stage, the fact that CDT was not elevated above the standard laboratory cutoff in our sample is consistent with prior reports of rapid decline in CDT levels in as little as eight days after cessation of drinking (Bell, Tallaksen et al. 1993
As mentioned earlier in this paper, observational studies have found consistent associations with alcohol and HCV transmission. The cause for this is multifactorial, but alcohol’s known psychological effects (i.e. disinhibition, loss of judgment, mood elevation or depression), can lead to engagement in high-risk sexual and drug taking behaviors.
Although previously cited observational studies find that alcohol is an independent risk factor for HCV infection, it is obvious that alcohol use per se is not a mode of transmission of HCV. What can be inferred however is that alcohol use, especially chronic, heavy alcohol use, may be associated with isolated high-risk behaviors in certain populations, which in turn increase the risk for HCV infection.
At the time a drinker, usually in their fourth or fifth decade of life, comes in for treatment of primary alcoholism, high-risk behaviors associated with HCV transmission may have occurred as isolated or infrequent incidents in the remote past (i.e. experimental IDU or sexual promiscuity during early adulthood). It seems unlikely that subjects will report such behavior at the time of entry into treatment for alcoholism, as such events are temporally remote from the current treatment episode, and are of a highly sensitive nature.
Our data are consistent with prior literature reporting that alcoholic cohorts have a high prevalence of HCV infection and engage in high-risk behavior for transmission of blood-borne infections (Avins, Woods, Lindan, et al. 1994
; Boscarino, Avins, Woods, et al. 1995
; Stein, Hanna, Natarajan, et al. 2000
; Malow, Devieux, Jennings, et al. 2001
). In particular, IDU and needle sharing are quite common in our Philadelphia study populations. Previous studies have reported increased rates of IDU in alcoholics with HCV, but our data may offer additional insights into this problem as we were able to compare our treatment seeking alcoholic population to a lower functioning, treatment seeking alcohol and cocaine dependent population. The lack of a significant difference in overall prevalence of HCV and HCV risk behaviors between these two populations that seem disparate on the surface suggests that alcohol dependent individuals seeking outpatient treatment may, in fact, be at the same high risk for HCV infection as subjects with both cocaine and alcohol dependence.
Although sexual promiscuity and blood transfusions have been identified as primary routes of transmission for HCV, our analysis did not show them as independent risk factors in our population. This is most likely due to limitations in our assessment of these behaviors. There is no standard risk threshold for HCV transmission from sexual activity, but CDC has reported increased risk for HCV in persons with ten to fifty or more lifetime sexual partners (Centers for Disease Control and Prevention 1998
; Alter, Kruszon-Moran, Nainan, et al. 1999
). The version of the RAB we used did not have items allowing for precise quantification of lifetime sexual partners, thus we were not able to obtain a measure of sexual behavior consistent with the threshold reported by CDC.
In regard to blood transfusions, the RAB did not assess the frequency or year in which the subject received a blood transfusion. The studies reported here did screen out individuals with serious medical conditions, which would require multiple blood transfusions (i.e. hemophilia or renal dialysis). Since the blood supply in the United States has been effectively screened for HCV since the early 1990s, any person receiving a blood transfusion over the last 14 years is unlikely to have contracted HCV via this route. Our study therefore likely screened out those individuals at highest risk for transfusion-borne HCV.
There are five main limitations for the findings from this study. First, these data were taken from two clinical trials of pharmacotherapies for alcohol (Study I) and combined alcohol and cocaine dependence (Study II). Such trials have strict inclusion/exclusion criteria which exclude individuals such as those with other substance dependence (e.g., opioids), as well as those with serious or unstable medical or psychiatric disorders. As such, these findings are most relevant to other medication trials similar to these, but less relevant to the population of alcohol or alcohol and cocaine dependent individuals as a whole.
Second, as HCV status was established only by HCV-EIA without confirmatory HCV RNA testing, it is possible that a proportion of the subjects with HCV positive serostatus had mounted an immune response to the HCV infection, and thus were currently disease free. Although such RNA analyses are costly, it is important that future studies examine HCV seropositive subjects both with and without active disease to further establish the impact of HCV on alcohol use biomarkers.
Third, fifty-nine subjects or roughly 14% were excluded from the analysis due to missing data or falling outside the ten-day acute phase recovery window. However, the missing data was proportional in each study group.
Fourth, we only examined baseline data, which eliminates our ability to examine any impact that HCV status may have on alcohol biomarkers during treatment for alcohol dependence. As such alcohol biomarkers are used in both standard outpatient treatment and clinical research settings to monitor alcohol use (Allen and Litten 2001
; Anton, Lieber, Tabakoff 2002
), it is important to determine what impact HCV serostatus has on these biomarkers during periods of abstinence and alcohol use. Finally, these studies did not specifically assess factors such as nutritional status or other liver disease, which could potentially confound the relationship between HCV serostatus and alcohol use biomarkers. As such, additional studies that assess nutrition, as well as other liver diseases would add substantially to the study of the impact of HCV on alcohol biomarkers.
Our results suggest that undiagnosed HCV infection is significantly associated with elevated transaminase levels. Interpretation of these biomarkers when HCV status is unknown could therefore be skewed in the direction of over-reporting alcohol use or alcohol-related hepatic inflammation, especially when relying on lab cut-off values of AST, ALT and GGT.
The data presented here draw attention to the need for HCV risk assessment in medication trials for alcohol dependence in which AST, ALT, GGT and CDT will be used as markers of alcohol consumption. As routine screening for HCV at time of study entry may be impractical, detailed HCV risk assessment could provide a cost conscious guide for determining when screening for HCV is most appropriate.